Trauma-Related Guillain-Barré Syndrome: Systematic Review of an Emerging Concept.

Guillain-Barré syndrome (GBS) is mainly associated with preceding exposure to an infectious agent, although the precise pathogenic mechanisms and causes remain unknown. Increasing evidence indicates an association between trauma-related factors and GBS. Here, we performed a systematic review, summarized the current scientific literature related to the onset of GBS associated with trauma, and explored the possible pathogenesis. A literature search of various electronic databases was performed up to May 2020 to identify studies reporting diverse trauma-related triggers of GBS. Data were extracted, summarized descriptively, and evaluated with respect to possible mechanisms. In total, 100 publications, including 136 cases and 6 case series involving GBS triggered by injury, surgery, intracranial hemorrhage, and heatstroke, met our eligibility criteria. The median age of the patients was 53 [interquartile range (IQR) 45-63] years, and 72.1% of the patients were male. The median number of days between the trigger to onset of GBS symptoms was 9 (IQR 6.5-13). Overall, 121 patients (89.0%) developed post-injury/surgical GBS, whereas 13 (9.6%) and 2 (1.5%) patients had preexisting spontaneous intracranial hemorrhage and heatstroke, respectively. The main locations of injury or surgeries preceding GBS were the spine and brain. Based on available evidence, we highlight possible mechanisms of GBS induced by these triggers. Moreover, we propose the concept of "trauma-related GBS" as a new research direction, which may help uncover more pathogenic mechanisms than previously considered for typical GBS triggered by infection or vaccination.

The Golgi Apparatus May Be a Potential Therapeutic Target for Apoptosis-Related Neurological Diseases.

Increasing evidence shows that, in addition to the classical function of protein processing and transport, the Golgi apparatus (GA) is also involved in apoptosis, one of the most common forms of cell death. The structure and the function of the GA is damaged during apoptosis. However, the specific effect of the GA on the apoptosis process is unclear; it may be involved in initiating or promoting apoptosis, or it may inhibit apoptosis. Golgi-related apoptosis is associated with a variety of neurological diseases including glioma, Alzheimer's disease (AD), Parkinson's disease (PD), and ischemic stroke. This review summarizes the changes and the possible mechanisms of Golgi structure and function during apoptosis. In addition, we also explore the possible mechanisms by which the GA regulates apoptosis and summarize the potential relationship between the Golgi and certain neurological diseases from the perspective of apoptosis. Elucidation of the interaction between the GA and apoptosis broadens our understanding of the pathological mechanisms of neurological diseases and provides new research directions for the treatment of these diseases. Therefore, we propose that the GA may be a potential therapeutic target for apoptosis-related neurological diseases.

Clinical Characteristics and Short-Term Prognosis of Autoimmune Encephalitis: A Single-Center Cohort Study in Changsha, China.

Background and Purpose: The incidence and prevalence of autoimmune encephalitis is gradually increasing. This retrospective observational study primarily aimed to analyze the clinical characteristics of autoimmune encephalitis patients in the Second Xiangya Hospital and report patient prognoses after immunotherapy. Methods: The clinical data of 86 patients who were diagnosed with autoimmune encephalitis from October 2014 to September 2018 were collected, and their corresponding clinical characteristics, laboratory examination, treatment, and outcome data analyzed. Results: In our study, 72 patients (83.7%) were positive for anti-NMDAR (N-methyl-D-aspartate receptor) antibody; 5 patients (6%) for anti-GABABR (γ-aminobutyric acid receptor-A); 4 patients (4.7%) for anti-LGI1 (leucine-rich, glioma inactivated 1); 3 patients (3.5%) for anti-Caspr2 (contactin-associated protein-like 2) (1 patient was positive for both anti-LGI1 and anti-Caspr2 antibodies); and 3 patients (3.5%) for onconeural antibodies. Among the 86 patients diagnosed as having autoimmune encephalitis, 50% showed acute disease onset (≤2 weeks). The most common inducing factor was fever or cold (17/86, 19.8%). The main clinical symptoms included, among others, psychiatric disturbances (82.5%), epilepsy (60.5%), autonomic dysfunction (58.1%), sleep disorders (45.3%), consciousness disorders (45.3%), and speech disorders (46.5%). No significant correlation between ICU admission rates and CSF or serum antibody scores was observed. However, CSF antibody scores of (+ + +) and (++) were associated with longer lengths of hospitalization (p < 0.05) and a higher CSF WBC count when compared with CSF antibody scores of (+) in patients with anti-NMDAR encephalitis (p < 0.05). Additionally, there was no significant correlation between mRS score difference on admission and discharge (after immunotherapy) and age, sex, and choice of immune treatment, while immune therapy taken within 15 days from onset was more inclined to be associated with an mRS score difference ≥2 after immunotherapy in patients with anti-NMDAR encephalitis (p = 0.006). Conclusions: Autoimmune encephalitis has an acute or sub-acute onset and presents with psychotic symptoms, epilepsy, and autonomic dysfunction. The sex ratio in anti-NMDAR encephalitis was nearly balanced. Infection was a major factor inducing anti-NMDAR encephalitis, and the CSF antibody scores could be helpful in determining its prognosis since these scores showed associations with hospitalization duration and CSF WBC counts.

Direct detection of Exophiala and Scedosporium species in sputa of patients with cystic fibrosis.

Detection of species of Exophiala and Scedosporium in the respiratory tracts of cystic fibrosis (CF) patients remains controversial because of highly variable results. The results of our study suggested a significantly higher prevalence and more complex colonization than previously estimated. Approximately 17% (27/162) of clinical sputum samples were found to be positive for Exophiala dermatitidis and 30% (49/162) were positive for Scedosporium apiospermum / S. boydii species complex determined by reverse line blot (RLB) hybridization. In contrast, only 14.2% (23/162) and 1.2% (2/162) of clinical sputa were positive for E. dermatitidis and S. apiospermum / S. boydii species complex when tested by culture, respectively. Molecular detection methods, such as loop-mediated isothermal amplification (LAMP) or reverse line blot (RLB) hybridization, have the potential to become powerful alternatives to selective culture, providing a more realistic understanding on the prevalence of E. dermatitidis and S. apiospermum / S. boydii species complex in the respiratory tract of CF patients.

The Formation Mechanism of Hydrogels.

Hydrogels are degradable polymeric networks, in which cross-links play a vital role in structure formation and degradation. Cross-linking is a stabilization process in polymer chemistry that leads to the multi-dimensional extension of polymeric chains, resulting in network structures. By crosslinking, hydrogels are formed into stable structures that differ from their raw materials. Generally, hydrogels can be prepared from either synthetic or natural polymers. Based on the types of cross-link junctions, hydrogels can be categorized into two groups: the chemically cross-linked and the physically cross-linked. Chemically cross-linked gels have permanent junctions, in which covalent bonds are present between different polymer chains, thus leading to excellent mechanical strength. Although chemical cross-linking is a highly resourceful method for the formation of hydrogels, the cross-linkers used in hydrogel preparation should be extracted from the hydrogels before use, due to their reported toxicity, while, in physically cross-linked gels, dissolution is prevented by physical interactions, such as ionic interactions, hydrogen bonds or hydrophobic interactions. Physically cross-linked methods for the preparation of hydrogels are the alternative solution for cross-linker toxicity. Both methods will be discussed in this review.

Tuberculosis/cryptococcosis co-infection in China between 1965 and 2016.

Cases of tuberculosis/cryptococcosis co-infection are rapidly increasing in China. However, most studies addressing this co-infection have been published in Chinese journals, and this publication strategy has obscured this disease trend for scientists in other parts of the world. Our investigation found that 62.9% of all co-infection cases worldwide were reported in the Chinese population (n=197) between 1965 and 2016, and 56.3% of these Chinese cases were reported after 2010. Nearly all cases originated from the warm and wet monsoon regions of China. HIV-positive subjects tended to correlate with more severe manifestations of a tuberculosis/cryptococcosis co-infection than those without HIV. Notablely, dual tubercular/cryptococcal meningitis was the most frequent (54.0%) and most easily misdiagnosed (95.2%, n=40/42) co-infection. We also found that the combined use of cerebrospinal fluid pressure and concentrations of glucose, protein and chlorine might be an inexpensive and effective indicator to differentiate tubercular/cryptococcal co-infection meningitis from tubercular meningitis and cryptococcal meningitis.

The Pleiotropic Effects of PPARs on Vascular Cells and Angiogenesis: Implications for Tissue Engineering.

Angiogenesis is a complex process in which capillaries are produced from blood vessels that already exists. Endothelial cells (ECs) and endothelial progenitor cells (EPCs) are pivotal for this process and for the maintenance/restorage of the endothelium. Decreased numbers and dysfunction of these cells have been related to growing cardiovascular risks. Peroxisome-proliferator-activated receptor (PPAR) is a large family of nuclear receptors, characterized by three isotypes: α, ß and γ. Numerous studies have shown that PPAR activation is involved in the pathology of a wide range of cardiovascular diseases and has a role in endothelial function, thrombosis and inflammation, etc., suggesting that PPAR agonists may be good candidates to treat the cardiovascular disease. However, controversial results exist on whether this nuclear receptor is inductive or depressive in the process of angiogenesis. Herein, this review will provide a detailed discussion of the up-to-date investigation of the role of PPARs in angiogenesis, with particular reference to their effects on angiogenesis-related cells--i.e., ECs, EPCs, vascular smooth-muscle cells (VSMCs), macrophages and endometrial cells--and will discuss the current and potential future applications of PPAR activators.

Physiological oxygen tension modulates soluble growth factor profile after crosstalk between chondrocytes and osteoblasts.

OBJECTIVES: Physiological oxygen tension plays a critical role in homoeostatic maintenance and development of endochondral bone. Based on the proximity between uncalcified cartilage and subchondral bone, and microchannels that serve as a message delivery network between them, we aimed to explore the influence of low oxygen tension on soluble factor secretion in both chondrocytes and osteoblasts, after co-culture. MATERIALS AND METHODS: Contact co-culture was achieved for morphological observation using red fluorescent protein (RFP)-labelled chondrocytes and green fluorescent protein (GFP)-labelled osteoblasts, and non-contact co-culture achieved by transwell chambers. This was used to screen genetic variation of growth factors in hypoxia, including respective phenotypic markers, factors involving hypoxia and angiogenesis relationships, bone morphogenetic family proteins, and other general factors. RESULTS: We observed a significant increase in chondrocyte size following co-culture, in both normoxia and hypoxia, but not of osteoblasts. Expression of Aggrecan in chondrocytes and alkaline phosphatase in osteoblasts was down-regulated under hypoxia following co-culture. Under hypoxia, we found that expression of hypoxia-inducible factor-1α, vascular endothelial growth factor-A/B, VE-cadherin, bone morphogenetic protein-2, and insulin-like growth factor-1 in chondrocytes, increased, but HIF-1α, platelet-derived growth factor, BMP-5/-6 and fibroblast growth factor-1 in osteoblasts, decreased. CONCLUSIONS: These results not only indicate the importance of crosstalk between chondrocytes and osteoblasts but also improve our understanding of the mechanisms underlying homoeostatic maintenance of endochondral bone.

Peroxisome Proliferator-Activated Receptor (PPAR) in Regenerative Medicine: Molecular Mechanism for PPAR in Stem Cells' Adipocyte Differentiation.

Regenerative medicine plays an indispensable role in modern medicine and many trials and researches have therefore been developed to fit our medical needs. Tissue engineering has proven that adipose tissue can widely be used and brings advantages to regenerative medicine. Moreover, a trait of adipose stem cells being isolated and grown in vitro is a cornerstone to various applications. Since the adipose tissue has been widely used in regenerative medicine, numerous studies have been conducted to seek methods for gaining more adipocytes. To investigate molecular mechanism for adipocyte differentiation, peroxisome proliferator-activated receptor (PPAR) has been widely studied to find out its functional mechanism, as a key factor for adipocyte differentiation. However, the precise molecular mechanism is still unknown. This review thus summarizes recent progress on the study of molecular mechanism and role of PPAR in adipocyte differentiation.

Poly(3-hydroxybutyrate-co-4-hydroxybutyrate) Based Electrospun 3D Scaffolds for Delivery of Autogeneic Chondrocytes and Adipose-Derived Stem Cells: Evaluation of Cartilage Defects in Rabbit.

The management of chondral defects has long been a challenge because of the poor self-healing capacity of articular cartilage. Many approaches ranging from symptomatic treatment to structural cartilage regeneration have obtained very limited satisfactory results. Cartilage tissue engineering, which involves an optimized combination of novel scaffolds, cell sources and growth factors, has emerged as a promising strategy for cartilage regeneration and repair. In this study, the cellular morphologies and the adhesion, migration and proliferation capabilities of adipose-derived stem cells (ASCs) and chondrocytes seeded on 3D scaffolds composed of electrospun poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P3HB4HB) were evaluated. Next, TGF-ß1/scaffolds with 4:1 co-culture of ASCs and chondrocytes were implanted into the full thickness cartilage defects in rabbit knee for 16 weeks. ASCs and chondrocytes seeded on the scaffolds showed better adhesion, migration and proliferation than that on petri dishes in vitro. Importantly, implantation with TGF-ß1/scaffolds with delivery of ASCs and chondrocytes revealed desirable in vivo healing outcomes. These results demonstrate that ASCs have great potential in the field of tissue engineering. It is possible that the improvement in ASC-seeded electrospun 3D P3HB4HB scaffolds may ultimately lead to improved repair of cartilage injuries.

Gene profile of soluble growth factors involved in angiogenesis, in an adipose-derived stromal cell/endothelial cell co-culture, 3D gel model.

OBJECTIVES: The aim of this study was to investigate gene expressions of growth factors for angiogenesis, in a three-dimensional (3D) gel populated with adipose-derived stromal cells (ASCs) and endothelial cells (ECs) in co-culture. MATERIALS AND METHODS: The 3D gel, mixed with green fluorescent protein (GFP)-positive ASCs and DsRed-Express-positive ECs, 1:1 ratio, was established in vitro. The phenomenon of angiogenesis was observed using confocal microscopy. To detect gene expressions for growth factor proteins in both ASCs and ECs, transwell co-culture was used, and cell lysate samples were collected at 1, 3, 5 and 7 days. Semi-quantitative polymerase chain reaction (PCR) was conducted to quantify mRNA expressions of the growth factors. RESULTS: Angiogenesis was first observed in the gels by 7 days post-implantation. Over this time in ECs, genes coding for VEGFA/B, IGF-1, HIF-1α, FGF-1/-2 and BMP-5/-7 significantly increased. Meanwhile in ASCs, genes coding for VEGFA/B, IGF-1, HIF-1α, FGF-1/-2 and BMP-6 also were significantly enhanced. In particular, increased amounts of IGF-1 and HIF-1α in both ECs and ASCs were prominent relative to other factors. CONCLUSIONS: Contact co-culture with ASCs and ECs at 1:1 ratio, in the 3D gel promoted angiogenesis; non-contact co-culture further confirmed gene expressions for growth factors, VEGFA/B, IGF-1, HIF-1α and FGF-1/-2 in both ASCs and ECs; BMP-5/-7 in ECs and BMP-6 in ASCs were also confirmed. This establishment of growth factor expression seemed to be responsible for enhancement of angiogenesis. This indicates that these factors could be utilized as targets for engineered angiogenesis.

Miscellaneous animal models accelerate the application of mesenchymal stem cells for cartilage regeneration.

Disorders in articular cartilage affect many people, and are one of the leading causes of infirmity and decreased quality of life in adults. Tissue engineering and regenerative medicine related to cartilage include a broad range of settings and approaches that seek to repair, augment, replace or regenerate cartilage tissue. Formation of new tissue by cartilageforming cells (chondrogenic cells) is a central feature of each of these goals. Mesenchymal stem cell (MSC) transplantation has been introduced to avoid some of the side-effects and complications of current techniques. Different mesenchymal stem cell sources possess different abilitties to regenerate cartilage. However, the use of MSCs for cartilage repair is still at the stage of preclinical and phase I studies, and no comparative clinical studies have been reported. Therefore, it is difficult to make conclusions in human studies. The focus of this review is the role of MSCs, from different sources in which animal models were involved, in tissue-engineering cartilage repair, and research findings aimed at exploring a more rational application of animal models as the basis for future research, with clinical transformation providing a context.

Potential replication of induced pluripotent stem cells for craniofacial reconstruction.

The craniofacial region contains many specified tissues, including bone, cartilage, muscle, blood vessels, fat, skin and neurons. A defect or dysfunction of the craniofacial tissue after post-cancer ablative surgery, trauma, congenital malformations and progressive deforming skeletal diseases has a huge influence on the patient's life. Therefore, functional reconstruction of damaged tissues is highly sought. The use of cell-based therapies represents one of the most advanced methods for enhancing the regenerative response for craniofacial wound-healing. The recently acquired ability to reprogram human adult somatic cells to induced pluripotent stem cells (iPSCs) in culture may provide a powerful tool for in vitro disease modeling and an unlimited source for cell replacement therapy. This review focuses on the generation, biological characterization and discussion of the potential application of iPSCs for craniofacial tissue-engineering applications.

Anti-proliferative and pro-apoptotic effect of carvacrol on human hepatocellular carcinoma cell line HepG-2.

Carvacrol is one of the members of monoterpene phenol and is present in the volatile oils of Thymus vulgaris, Carum copticum, origanum and oregano. It is a safe food additive commonly used in our daily life, and few studies have indicated that carvacrol has anti-hepatocarcinogenic activities. The rationale of the study was to examine whether carvacrol affects apoptosis of human hepatoma HepG2 cells. In this study, we showed that carvacrol inhibited HepG2 cell growth by inducing apoptosis as evidenced by Hoechst 33258 stain and Flow cytometric (FCM) analysis. Incubation of HepG2 cells with carvacrol for 24 h induced apoptosis by the activation of caspase-3, cleavage of PARP and decreased Bcl-2 gene expression. These results demonstrated that a significant fraction of carvacrol treated cells died by an apoptotic pathway in HepG2 cells. Moreover, carvacrol selectively altered the phosphorylation state of members of the MAPK superfamily, decreasing phosphorylation of ERK1/2 significantly in a dose-dependent manner, and activated phosphorylation of p38 but not affecting JNK MAPK phosphorylation. These results suggest that carvacrol may induce apoptosis by direct activation of the mitochondrial pathway, and the mitogen-activated protein kinase pathway may play an important role in the antitumor effect of carvacrol. These results have identified, for the first time, the biological activity of carvacrol in HepG2 cells and should lead to further development of carvacrol for liver disease therapy.